Stretch‐evoked inhibition of spontaneous migrating contractions in a whole mount preparation of the guinea‐pig upper urinary tract

1 The effects of circumferentially‐applied stretch on the spontaneous contractility of a whole mount preparation of the guinea‐pig upper urinary tract (UUT) (renal pelvis and ureter) were investigated by use of standard isometric tension recording techniques. 2 Simultaneous tension recordings of the proximal and distal portions of the renal pelvis (RP) and ureter revealed that spontaneous contractions, in 79% (n=66) of preparations, originated in the proximal RP (at a frequency of 4.5 min−1) and propagated to the distal RP and ureter at a velocity of 1–3 cm s−1. Pretreatment with tetrodotoxin (TTX) (3–10 μM) or NG‐nitro‐L‐arginine (100 μM) had little effect on the spontaneous contractility of the UUT, motility indexes (MIs) (contraction amplitude×contraction frequency) calculated after 20 min exposure were little affected by TTX or NG‐nitro‐L‐arginine (L‐NOARG). ω‐Conotoxin GVIA (100 nM) significantly reduced MI values in both the proximal RP and ureter. 3 Exposure of the spontaneously‐active UUT to capsaicin (10 μM for 15 min) induced a transient increase in UUT contractility, followed by a prolonged negative inotropic effect. The MI values, calculated 60 min after the washout of capsaicin, for the proximal and distal RP and ureter were reduced to 56%, 53% (n=18) and 61% (n=16), respectively, of their control values. This capsaicin pretreatment blocked the positive inotropic effects of transmural electrical nerve stimulation on UUT contractility to reveal a small inhibitory effect which was readily blocked by tetrodotoxin (3 μM) (n=3). The excitatory and inhibitory actions of nerve stimulation were both blocked by TTX (3 μM) 4 A second exposure to capsaicin (10 μM for 15 min), further reduced the MI values (calculated 60 min after washout) in the proximal and distal RP to 41% and 31%, respectively (n=6; P